It is well known that ruminants are in need of bioavailable essential amino acids in order to perform well as domesticated livestock. In this regard, if the animal, for example a dairy cow, does not have its minimum requirements of essential amino acids such as lysine and methionine, the animal will not produce milk at optimum yield, and its health may be in general decline.
Providing essential amino acids to ruminants is not as simple as it sounds. For example, the bacteria in the rumen of a cow are known to routinely degrade amino acid sources, like lysine and methionine. Put another way, the bacteria in the rumen metabolize the amino acid source and thus “rob” the animal of the benefit of the amino acid. By the time metabolized byproduct passes from the rumen into the intestine, the amino acid is gone. The challenge, therefore, is to develop products which will allow the amino acid to be stable in the rumen, but capable of absorption when it passes from the rumen into the intestine. In other words, the essential amino acids, such as lysine and methionine, need to be bioavailable only in the intestine, and remain stable and therefore not metabolized in the rumen.
In the past, this problem has been recognized, and feed developers have used fats, minerals, carbohydrates and binders to protect amino acids from rumen degradation. This technology involves simple coating of the material in hopes that the coated amino acid is rumen stable. Recently, Rhone Poulenc has provided a pH-sensitive polymer coating. The theory of a pH-sensitive polymer coating for the amino acid revolves around the pH differential between the rumen and the intestine. The rumen, for example, typically has a pH of 5.5 to 7.0, and the intestine a pH of 2-3. The theory of polymer-coated essential amino acids is that something which is stable as a coating at 5.5 to 7.0 (the rumen pH), but will solubilize at more acid pH's of the intestine (pH 2-3), should be stable in the rumen, but available in the intestine.
Both technologies used in the past, i.e. coatings, such as fat coatings, and the more recently developed pH-sensitive polymer coatings, have met with limited success and have some problems. The primary problem with any product relying upon coatings of any kind for rumen stability is that the coating can become abraded during handling and during chewing by the animal. If the process handler disturbs the coating, then the amino acid becomes available to microbes in the rumen and consumed, and therefore wasted by the animal. Likewise, if the animal abrades the coating during chewing, it then becomes available in the rumen for rumen bacteria to metabolize, and is therefore also wasted to the animal. Additionally, fat-protected or coated essential amino acids rely upon the fat resistance to enzymes in the rumen that are capable of digesting the protective fat coat, and, on the other hand, the ability of digestion by enzymes post-rumenally. However, if there is not a proper balance between resistance to attack in the rumen and digestion in the intestine, then the amino acid benefit to the animal may be lost.
From the above description, it can be seen that there is a real and continuing need for the development of products for delivery of essential amino acids to ruminant animals in a form that allows the material to be rumen stable, i.e. resistant to degradation in the rumen, but yet after delivery from the rumen to the intestine, highly absorbable and bioavailable in the intestine. It is a primary objective of this invention to improve upon available products to fulfill this need safely, effectively, efficiently and at low cost.
In the prior Zinpro Corporation patent by Michael Anderson, it was discovered that calcium or magnesium complexed salts of certain amino acids could be used to prepare a bypass rumen product. This invention takes a different attack on the problem with specificity of improving the availability of essential amino acids in ruminants.
Lysine is an essential amino acid in the diet of mammals. That is, lysine cannot be synthesized by mammals at a rate adequate to meet metabolic requirements and so must be supplied in the diet. Corn (Zea mays L.) is notoriously low in lysine and, if used in a single grain ration, requires lysine supplementation both to maintain animal health and to achieve economical animal growth. Protected lysine imine derivatives are disclosed in copending, concurrently filed, commonly assigned case, Stark et al. entitled RUMEN PROTECTED LYSINE.
The present invention extends the above referenced technology to other limiting and/or essential amino acids, by forming compounds which are essentially immune to attack by the microbes in the rumen but can still be digested and absorbed through the intestine wall to allow a highly bioavailable form of essential amino acids that are surprisingly immune from rumen organism attack. Structures of the compounds prepared are centered around the imine of the essential amino acids (Schiff's base).
In the past, there have been some alpha imine and epsilon imine derivatives of lysine investigated for biologically available active derivatives for rats. See for example, Finot, N-Substituted Lysines As Sources of Lysine in Nutrition, Adv. Exp. Med. Bio. 1978; 105:549-570; Nutritional Improvement of Food and Feed Proteins, edited by Friedman, published at Plenum, N.Y., and Finot et al., Availability of the true Schiff's bases of lysine. Chemical Evaluation of the Schiff's Base Between Lysine and Lactose in Milk, Adv. Exp. Med. Biol. 1977; 86B:343-365. The first Finot article concludes that the biological availability of derivatives were four to seven times less reactive than free lysine in the Maillard reaction and could therefore be subjected to heat. The second article deals with chemical evaluation of the Schiff's base between lysine and the lactose in milk. There is no teaching in either article of any compounds having usefulness of providing stability of lysine derivatives in the rumen or providing compounds which can be successfully absorbed through the intestine after passing through the rumen to assure that lysine will be available to the animal for diet supplementation of this important essential amino acid. There is also no teaching relating to other essential amino acids beyond lysine.
It is therefore another primary objective to provide diet supplements of ruminants to provide essential amino acid supplementation for animals that often use as a major grain ration corn (known to be notoriously low in lysine and methionine). As a result, overall economic growth of the animal can be enhanced, and enhanced in a manner which assures that the expense of essential amino acid supplementation will go to the animal and not be “robbed” (so to speak) by the microbes in the rumen as the material passes through the rumen.
The method of achieving the above objectives with certain chemical structures premised around imine (Schiff's base) of the essential amino acids is another primary objective of the invention.
Yet another objective of the present invention is to provide compounds which can be utilized to achieve successfully a rumen bypass an essential amino acid supplement that does not rely upon encapsulation and one which employs compounds that are easily processible in feed forms.
A still further objective is to provide methionine and histidine and other essential amino acid supplements that are rumen protected.